Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel

• Published in: Journal of materials science. Materials in medicine Vol. 23; no. 1; pp. 25 - 35
• Main Authors: Dong, Yixiao, Hassan, Waqar, Zheng, Yu, Saeed, Aram Omer, Cao, Hongliang, Tai, Hongyun, Pandit, Abhay, Wang, Wenxin
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Boston Springer US 2012; Springer; Springer Nature B.V
• Subjects: Acids; Animals; Biological and medical sciences; Biomaterials; Biomedical Engineering and Bioengineering; Biomedical materials; Cells, Cultured; Ceramics; Chemistry and Materials Science; Composites; Cross-Linking Reagents - chemistry; Glass; Hot Temperature; Hyaluronic Acid - chemistry; Hydrogels; Materials Science; Medical sciences; Natural Materials; Polymer Sciences; Polymers; Polymers - chemistry; Rabbits; Regenerative Medicine/Tissue Engineering; Surfaces and Interfaces; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Thin Films; Atom Transfer Radical Polymerization; Lower Critical Solution Temperature; Hyaluronic Acid; Interpenetrate Polymer Network; Copolymer Solution; Polyelectrolyte; In situ; Glycosaminoglycan; Oside polymer; Biomaterial; Hydrogel; Semiinterpenetrating polymer network; Hyaluronic acid; Branched copolymer; Composite material; Biomedical engineering
• ISSN: 0957-4530; 1573-4838
• DOI: 10.1007/s10856-011-4496-z

Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an ‘one pot and one step’ in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M n  = 258 g mol −1 ), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M n  = 475 g mol −1 ) and (2-methoxyethoxy) ethyl methacrylate (MEO 2 MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models.